The germinative cells of oral mucosa and epidermis differentiate into spinous, granular and keratinized cells sequentially. Keratohyalin granules (KHG) are a distinctive component of the granular layer, but the fully keratinized cells contain only filamentous proteins embedded in a matrix. The aim of this proposal is to determine the role of keratohyalin in normal keratinization in mammalian oral mucosa and epidermis. A prominent nonfilamentous basic protein has been isolated from the keratinized epidermis of newborn rats. This protein has biochemical properties consistent with its function as the interfilamentous matrix of keratin. Labeling studies and biochemical analyses have led to the postulate that a precursor protein of slightly greater molecular weight is cleaved by a specific protease in the conversion to the final basic protein of keratin. The precursor will be isolated to test this hypothesis. Immunoperoxidase studies with antibody to the basic protein show localization in the keratinized cells and in KHG in epidermis and oral epithelium. The cross-reactive protein in KHG may be the biochemically identified precursor protein. The basic protein is present in much lower amounts in oral epithelium than in epidermis. This difference may reflect differences in function of the various epithelia. The structural and potential enzymatic function of this protein relevant to oral epithelia will be investigated.